PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2

Passer, Brent J.; Cañelles, Matilde; Lefterov, Iliya; Ganjei, J. Kelly; Fowlkes, B. J.; Koonin, Eugene V.; D’Adamio, Luciano

doi:10.3233/jad-2001-3203

Cited by 63 publications

(38 citation statements)

References 46 publications

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“…Another stress-related transcript upregulated during migration codes for a rhomboid protease of the inner mitochondrial membrane, presenilin-associated rhomboid protease (PARL), originally named for its interaction with presenilin and its role in the processing of amyloid beta precursor protein (Pellegrini et al 2001). Recent data, however, indicates that PARL plays an important regulatory role in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Changes in brain gene expression during migration in the white-crowned sparrow

Jones

Pfister-Genskow

Cirelli

et al. 2008

Brain Research Bulletin

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Long-term recordings of seasonal sleep patterns in captive white-crowned sparrows (Zonotrichia leucophrys gambelii) have shown that these birds markedly reduce sleep time during the migratory period relative to the non-migratory period. It was also found that, despite this sleep reduction, sparrows showed no evidence of neurobehavioral deficits in a standard operant task used to assess the effects of sleep loss. In this study, we performed an extensive microarray analysis of gene expression in the sparrow telencephalon during the migratory season (M), relative to a 78-hour period of enforced sleep restriction during the non-migratory season (SR), and a 6-hour period of normal wakefulness during the non-migratory season (W). Of the estimated 17,100 transcripts that were reliably detected, only 0.17% changed expression as a function of M (relative to both SR and W), and 0.11% as a function of SR (relative to both M and W). Brain transcripts whose expression increased during M include the facilitated glucose transporter GLUT1, the presenilin associated rhomboid-like protein PARL, and several members of the heat shock protein family, such as HSP70, HSP90, GRP78 and BiP. These data suggest that migration is associated with brain cellular stress and enhanced energetic demands.

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Section: Discussionmentioning

confidence: 99%

Changes in brain gene expression during migration in the white-crowned sparrow

Jones

Pfister-Genskow

Cirelli

et al. 2008

Brain Research Bulletin

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“…25 This suggested the possibility that Opa1, like its yeast orthologue Mgm1p, undergoes posttranscriptional modification leading to its proteolytic cleavage and to the production of this shorter IMS form by Rbd1p, a rhomboid protease [63][64][65] whose orthologue in mammals is called Parl. 8 Rhomboids are a widely conserved polytopic-membraneprotein family. 66 In D. melanogaster they activate the epidermal growth factor (EGF) signalling pathway, by proteolytically cleaving the EGF receptor ligands Spitz, Gurken and Keren.…”

Section: Opa1 and The Cristae Remodelling Pathway In Apoptosismentioning

confidence: 99%

“…Members of the Parl subfamily, prototyped by Parl itself, have an extra TMH N terminus to the 6-TMH catalytic core, a '1 þ 6' structure. 8 These additional TMHs imply the existence of a loop connecting them to the 6-TMH catalytic core. The functional role of this domain remains unknown.…”

Section: Opa1 and The Cristae Remodelling Pathway In Apoptosismentioning

confidence: 99%

“…In the recent years this assumption has been subverted by two observations: mitochondrial network undergoes fragmentation and topology of the IM is altered in concurrence with the functional and proteomic changes occurring to the apoptotic mitochondrion. 7 These observations prompted several groups to investigate the mechanisms regulating mitochondrial morphology in healthy and dying cells and a new, unexpected player came into the game: a rhomboid protease of the inner mitochondrial membrane (IMM) called presenilin-associated rhomboid-like (Parl), originally identified in a yeast two-hybrid screen as an interactor of presenilin, 8 a protein involved in processing of the amyloid b-peptide. Here, we review the recent progresses in the regulation of mitochondrial shape during cell life and death, focusing on the role of this mitochondrial rhomboid protease.…”

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confidence: 99%

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A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis

Scorrano

2007

Cell Death Differ

132

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Mitochondria are crucial amplifiers of death signals. They release cytochrome c and other pro-apoptotic factors required to fully activate effector caspases. This release is accompanied by fragmentation of the mitochondrial reticulum and by remodelling of the internal structure of the organelle. Here we review data supporting the existence of a regulatory network in the inner mitochondrial membrane that includes optic atrophy 1 (Opa1), a dynamin-related protein, and presenilin-associated rhomboidlike (Parl), a rhomboid protease. Opa1 regulates remodelling of the cristae independent of its effect on fusion. Cristae remodelling conversely requires Parl, which participates in the production of a soluble form of Opa1 retrieved together with the integral membrane one in oligomers that are disrupted early during apoptosis. Parl itself is regulated by proteolysis to generate a cleaved form, which in turn modulates the shape of the mitochondrial reticulum. Cleavage of Parl depends on its phosphorylation state around the cleavage site, implicating mitochondrial kinases and phosphatases in the regulation of mitochondrial shape.

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“…PARL, presenilin-associated rhomboid-like, derives its name from being identified in a yeast two-hybrid screen for proteins that could interact with Alzheimer's presenilin protein (Pellegrini et al 2001), although this association does not occur physiologically. The first functions of a PARL protease were discovered in the budding yeast: early genome-wide screens revealed that its homolog of PARL, Pcp1 (also called Rbd1 and Ygr101w), is localized to mitochondria (Steinmetz et al 2002), and its deletion results in mitochondrial fragmentation (Dimmer et al 2002), but the basis was unclear.…”

Section: Rhomboid Proteins In Human Diseasementioning

confidence: 99%

Rhomboid proteins: conserved membrane proteases with divergent biological functions

Urban¹

2006

Genes Dev.

115

110

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The rhomboid gene was discovered in Drosophila, where it encodes a seven transmembrane protein that is the signal-generating component of epidermal growth factor (EGF) receptor signaling during development. Although metazoan developmental regulators are rarely conserved outside the animal kingdom, rhomboid proteins are conserved in all kingdoms of life, but the significance of this remains unclear. Recent biochemical reconstitution and high-resolution crystal structures have provided proof that rhomboid proteins function as novel intramembrane proteases, with a serine proteaselike catalytic apparatus embedded within the membrane bilayer, buried in a hydrophilic cavity formed by a protein ring. A thorough consideration of all known examples of rhomboid function suggests that, despite biochemical similarity in mechanism and specificity, rhomboid proteins function in diverse processes including quorum sensing in bacteria, mitochondrial membrane fusion, apoptosis, and stem cell differentiation in eukaryotes; rhomboid proteins are also now starting to be linked to human disease, including early-onset blindness, diabetes, and parasitic diseases. Regulating cell signaling is at the heart of rhomboid protein function in many, but not all, of these processes. Further study of these novel enzymes promises to reveal the evolutionary path of rhomboid protein function, which could provide insights into the forces that drive the molecular evolution of regulatory mechanisms.Developmental biology has progressed from descriptive observation to mechanistic analysis in the latter half of the 20th century (Wolpert 1998). Powerful genetic tools applied to model organisms have led to an intricate and beautiful picture of how genes build complex organisms. Parallel analyses in diverse animals and sequencing of their genomes revealed that a relatively small number of master genes and core regulatory pathways are used repeatedly in different contexts to build complex patterns, and these factors are conserved among animals.In addition to revealing some of the underlying logic of how organisms are constructed, these approaches were powerful in identifying the factors that mediate this intricate level of organization. But little is still known about how these key regulators exert their functions biochemically, which is central to understanding core biological processes that drive development at the molecular level.Most developmental regulators are conserved in the animal kingdom but are not found in other kingdoms, including plants, perhaps because plants and animals evolved multicellular development after splitting from a common ancestor (Meyerowitz 2002). But in recent years a small number of factors have been discovered that are conserved across kingdoms, raising the exciting possibility that they are key regulators that evolved very early. One such class of regulatory proteins are intramembrane proteases.Intramembrane proteolysis, the cleavage of membrane proteins within their membrane spanning segments, has recently been discovered to...

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PAMP and PARL, two novel putative metalloproteases interacting with the COOH-terminus of Presenilin-1 and -2

Cited by 63 publications

References 46 publications

Changes in brain gene expression during migration in the white-crowned sparrow

Changes in brain gene expression during migration in the white-crowned sparrow

A cut short to death: Parl and Opa1 in the regulation of mitochondrial morphology and apoptosis

Rhomboid proteins: conserved membrane proteases with divergent biological functions

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